MERIT-UC Interim Report – 2014

Report May 2014

So far we have screened 139 patients for the study and included 93 into the study. An interim analysis of the open label induction period was performed in January 2014. The main outcomes for 76 patients completing the open label induction period of 16 weeks are shown in Figure 1. We observed a 46% clinical response rate at week 16. This is remarkable since this endpoint reflects MTX monotherapy 4 weeks after all steroids are stopped at week 12. The steroid free clinical remission rate in MERIT-UC is currently 29%. These are very encouraging numbers, especially if you put this into context with another UC study with a week 16 endpoint – the recently published SUCCESS trial (Figure 2; Panaccione R et al. Combination Therapy With Infliximab and Azathioprine Is Superior to Monotherapy With Either Agent in Ulcerative Colitis. Gastroenterology 2014;146:392-400). The definitions of the endpoints in both studies slightly differ (see Figure 1 and Figure 2) and MERIT-UC also included anti-TNF and azathioprine failures, whereas SUCCESS included only anti-TNF naïve patients and patients who were off azathioprine for 3 months or never exposed to azathioprine. Overall the data of the open label induction period suggest that MTX has comparable efficacy to azathioprine or anti-TNF therapy to achieve a steroid free remission.

The Steering committee of MERIT-UC strongly feels that MTX is a good option for patients with active UC, but we definitely have to complete the trial to define this therapeutic option better in regard to maintenance of remission. Due to the concurrent sampling of DNA and sera we may also be able to predict response and remission with pharmacogenetic and pharmacokinetic analyses in the future. We encourage all sites to continue to actively recruit in the trial, which is the so far largest clinical trial study of the CRA. The currently projected target for the last patient entering the study is May 31 2015.

AIMS of MERIT-UC

MERIT-UC is a NIH funded multi-center prospective placebo controlled study to investigate the safety and efficacy of 25 mg MTX applied subcutaneously once weekly in patients with active UC, who are either steroid dependent or are intolerant or not responding to 5-ASA’s or azathioprine/6-mercaptopurine therapy or have no response/ lost response to infliximab prior to the study inclusion.

The aims of the trial are:

1) To evaluate the safety and tolerability of 25 mg MTX applied sq once weekly over a time period of 48 weeks.

2) To evaluate the relapse-free survival of MTX maintenance therapy compared to placebo over a time period of 32 weeks.

3) To evaluate the efficacy of MTX over a time period of 16 weeks to induce steroid free remission.

4) To establish a DNA, plasma and serum library to enable the evaluation of clinical and pharmacogenomic models to predict the response to MTX therapy in patients with UC.